[Klebsiella pneumoniae septicaemia and meningitis in a diabetic patient with an hepatic abscess]. / Septicémie et méningite à Klebsiella pneumoniae au depart d'un abcès hépatique chez un patient diabétique.

Klebsiella pneumoniae infections show particular features depending on the geographical localization as well as comorbidity factors. We are presenting the case of a european patient with diabetes mellitus who presented a septicaemia, a meningitis as well as an hepatic abscess due to a K. pneumoniae and whose evolution was excellent under antibiotics. Usually described among Asian patients, the primary hepatic K. pneumoniae abscess, which is a clinical entity recently described, can give rise to potentially serious and multiple septic metastasis. We also discuss the diagnostic and therapeutic attitudes related to this infection.

Antimicrobial therapy for intra-abdominal infections: guidelines from the Infectious Disease Advisory Board (IDAB).

Intra-abdominal infection is a common cause of severe sepsis in a hospital setting and remains associated with a significant morbidity, mortality and resource use. Early adequate surgery or drainage remain the cornerstones of intra-abdominal infection management and impact on patients outcome. Concomitant early and adequate empiric antimicrobial therapy further influences patients morbidity and mortality. Multiple empirical regimens have been proposed in this setting, but rarely supported by well designed, randomized-controlled studies. The current manuscript summarizes the recommendations of the Infection Disease Advisory Board on the management of intra-abdominal infections. Empiric antimicrobial therapy for the most common causes of abdominal infections is proposed. In addition, particular attention has been paid on antibiotic treatment duration.

Differential transferrin receptor density in human colorectal cancer: A potential probe for diagnosis and therapy.

Transferrin receptor density was investigated in human colorectal surgical specimens. Crude membranes were prepared from 23 cancer tumors (adenocarcinoma or malignant villous tumor) and 3 non-cancer tumors (polyadenoma or villous tumor) and 26 adjacent control mucosa. Contrary to non-cancer tumors, Scatchard analysis of 125I-transferrin binding data evidenced higher maximal transferrin binding capacity and lower dissociation constant in cancer tissues (Bmax cancer 1.828+/-0.320 nmol/g, Kd 24.1+/-4.7 nM), as compared to paired control colonic mucosa (Bmax contol 0.851+/-0.182 nmol/g, Kd 30.7+/-7.3 nM), paired t-tests: Bmax p<0.001, Kd p<0.05). As the cancer/control Bmax ratio was 2.6+/-0.4,transferrin carrier constructs should be proposed for cancer imaging or therapy.

[Dysfunction of the aldosterone synthesis pathway as a marker of malignity in symptomatic and asymptomatic adrenal masses]. / Du dysfonctionnement de la voie de synthèse de l'aldostérone comme marqueur de malignité des masses surrénaliennes symptomatiques et asymptomatiques.

Fundamental research performed in the author's laboratory led to the understanding of mechanisms of the mineralocorticoid biosynthetic pathway. Sensitive assays were then developed to allow measurement of the different mineralocorticoid metabolites in several biological fluids. Using these methods biological markers that contribute to the differential diagnosis between benign and malignant adrenal tumors were identified. In the present paper we report that the exploration of the entire mineralocorticoid pathway in the plasma of patients during basal state and after stimulation and/or inhibition test is a powerful tool to predict or validate diagnosis of adrenal malignancy. Moreover, mineralocorticoid exploration can help differentiate between two different types of malignancy, ie malignant cortical adrenaloma and metastases of other cancer. The biochemical mechanisms leading to the atypical mineralocorticoid metabolism in the case of malignant cortical adrenaloma are now under study.

Mechanisms of isoproterenol-induced atrial natriuretic peptide release from superfused rabbit atria.

The mechanisms for isoproterenol-induced atrial natriuretic peptide (ANP) release were studied in superfused rabbit sliced right atria. Addition of 1 microM norepinephrine to this preparation induced a significant monophasic twofold rise in ANP release. This effect was abolished by 1 microM propranolol and mimicked by 1 microM isoproterenol. Furthermore, addition of 200 microM 3-isobutyl-1-methylxanthine (IBMX) to the superfusing medium potentiated isoproterenol effect 31%. In addition, superfusion of slices with 0.5 mM N6,2-O-dibutyryladenosine 3',5'-cyclic monophosphate [(Bu)-2cAMP] enhanced ANP release in the same manner as the beta-agonist. After isoproterenol stimulation, adenosine 3',5'-cyclic monophosphate (cAMP) concentration in effluents increased significantly. ANP secretory response to isoproterenol was unaffected by extracellular calcium concentration or 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). Finally, 10 microM indomethacin significantly reduced isoproterenol-stimulated ANP release. It is concluded that 1) norepinephrine-induced ANP release is mediated by its beta-agonist activity, 2) isoproterenol-stimulated release appears to be mediated by cAMP, 3) isoproterenol effect does not require extracellular calcium, and 4) prostaglandins may be involved in this beta-adrenergic effect.

Hypoaldosteronism accompanied by normal or elevated mineralocorticosteroid pathway steroid: a marker of adrenal carcinoma.

In order to find a biochemical marker to assist the physician in the difficult differential diagnosis between malignant and nonmalignant adrenal tumors, plasma levels of the mineralocorticosteroids (deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, and aldosterone) were determined. The same method (RIA which is preceded by a crucial separation step) was used to measure all these steroids including aldosterone. The subjects included 15 adults presenting various clinical signs of adrenocortical tumors (histopathologically: 6 with adrenal carcinoma, 1 with a history of adrenal carcinoma, 1 with adrenal metastasis from other forms of cancer, 6 with adenoma, and 1 with hyperplasia). The results show that both presurgery and during a recurrence of adrenal carcinoma, hypoaldosteronism occurs which contrasts with the normal or even elevated levels of some aldosterone precursors. In the 7 cases of adrenal cortical carcinoma, this dysfunction of the aldosterone pathway was detected regardless of the impairment of the other steroidogenesis pathways, whereas it was never found with a nonmalignant tumor. Despite the limited number of cases so far available, these findings suggest that detection of abnormalities of the aldosterone pathway, and particularly the detection of hypoaldosteronism by an assay method involving a crucial steroid separating step, could contribute to a differential diagnosis between benign and malignant adrenocortical tumor and between adrenal metastasis and other forms of cancer.

The alpha 2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects.

Onset of sudden death, myocardial infarction, and stroke occurs more likely in the morning hours. Similarly, a morning increase in epinephrine-induced platelet aggregation was observed accompanied by an increase in plasma catecholamines. Inhibition of the morning increase in platelet aggregation would be of therapeutic benefit. In this study the effect of the selective alpha 2-adrenergic receptor antagonist yohimbine on platelet aggregation was evaluated in healthy subjects. Yohimbine administered orally selectively antagonized epinephrine but not collagen, arachidonic acid, or adenosine diphosphate-induced ex vivo platelet aggregation. The lowest dose of yohimbine that significantly inhibited epinephrine-induced platelet aggregation was 8 mg. The inhibitory effect of yohimbine on platelet aggregation lasted 10 hours with the 12 mg dose. At the doses studied (4, 8, and 12 mg), yohimbine did not modify blood pressure, standing heart rate, or plasma catecholamine or glucose concentrations. Twelve milligrams of yohimbine moderately but significantly accelerated supine heart rate (mean maximal increase, 7 +/- 3 beats/min). Further clinical studies are needed to evaluate whether bedtime administration of 12 mg yohimbine may block the morning increase in epinephrine-induced platelet aggregation.

Characteristics of atrial natriuretic hormone receptors in human pheochromocytomas.

The presence of functional receptors for human atrial natriuretic hormone in human pheochromocytomas was recently reported. The present study reports the binding of hANH as measured by Scatchard analysis in 4 human adrenal glands and in 5 human pheochromocytomas. Binding assays using [3H]ANH revealed a single class of high-affinity binding sites for hANH in both tissues. Human pheochromocytomas present a lower number of binding sites than normal human adrenal gland (Bmax of 7.1 +/- 2.1 vs 33.6 +/- 6.9 fmol/mg protein, respectively). However, the decreased number of ANH receptors was not paralleled by modifications of tissular cyclic GMP (cGMP). Moreover, plasma hANH concentrations in 7 patients with pheochromocytomas (20.2 +/- 2.7 pmol/l) were statistically higher than those obtained in 25 normal control humans (8.1 +/- 0.6 pmol/l, p less than 0.001). We also demonstrated the presence of immunoreactive ANH in the tumour itself.

Tissue distribution of 131I radiolabeled transferrin in the athymic nude mouse: localization of a human colon adenocarcinoma HT-29 xenograft.

The tissue distribution of 131I-transferrin (131I-Tf) was studied in athymic nude mice having s.c. human colonic adenocarcinoma HT-29 xenografts. Four days after 131I-Tf injection, the 131I-specific activity measured in the HT-29 tumor, i.e. amount of radioactivity per gram of fresh tissue, represented 0.31 +/- 0.09% of the injected radioactivity and was 1.90 fold more than that measured in the murine colon (P less than 0.05). After correction for intravascular 131I-Tf as estimated by means of 99mTc-Sn in vivo labeling of red blood cells, the 131I specific activity observed in the HT-29 tumor was 7.21 fold more than that observed in the murine colon. This subtracting method enabled us to localize a HT-29 tumor xenograft by gamma scintigraphy of the entire animal and demonstrated that 131I-Tf could be a non-specific but potent marker for human colon cancer.

Normal and growth hormone (GH)-secreting adenomatous human pituitaries release somatostatin and GH-releasing hormone.

Neuropeptides such as vasoactive intestinal peptide, LHRH, or TRH have been found in rat pituitary tissue and could act via paracrine or autocrine actions in this tissue. In this study we investigated whether normal human pituitary tissue and GH-secreting human pituitary adenomas could release somatostatin (SRIH) and GHRH. Fragments from three human pituitaries and dispersed cells from six GH-secreting adenomas (four adenomas were studied for GHRH release and five for SRIH release) were perifused using a Krebs-Ringer culture medium, and the perifusion medium was collected every 2 min (1 mL/fraction for 5 h). GH, GHRH, and SRIH were measured by RIA under basal conditions and in the presence of 10(-6) mol/L TRH or SRIH. Both normal pituitaries and GH-secreting pituitary adenomas released SRIH and GHRH. SRIH release commenced 90-180 min after initiation of the perifusion, at which time GH secretion had decreased significantly. TRH stimulated SRIH release from normal pituitary tissue and inhibited SRIH release from adenoma tissue. GHRH was present at the start of the perifusion, but rapidly disappeared. However, SRIH stimulated GHRH release from normal pituitary tissue, but not from adenoma tissue. Significant amounts of GHRH and SRIH were released during the experiments, suggesting their local synthesis. These results indicate that pituitary cells can release hypothalamic peptides. The liberation of these neuropeptides is regulated, and moreover, their regulation differs between normal and adenomatous pituitaries.

Salmonella endarteritis, about two cases and their management.

Mycotic aneurysms due to Salmonella are a classical but uncommon complication of Salmonella infections. We report two cases of such aneurysms, the first one having developed two successive aneurysms of the iliac arteries due to Salmonella typhimurium. The literature on Salmonella endarteritis is briefly reviewed. The importance of an aggressive surgical approach of the mycotic aneurysm, with removal of all infected material and extra-anatomic bypass through contaminated tissue is emphasized. The role of antibiotic treatment is also discussed.

Simultaneous determination of radio-immunoassayable methionine-enkephalin and radioreceptor-active opiate peptides in CSF of chronic pain suffering and non suffering patients.

Radio-immunoassayable methionine-enkephalin (ME) and radioreceptor-active opiate peptide levels (OP) were determined in CSF from patients, both with and without chronic pain, under investigation for vertebral disk disease. This study showed: that there was no direct correlation between ME and OP levels in CSF; OP levels were negatively correlated with the ME/OP ratio; migraine patients had higher levels of ME; ME concentrations were reduced in patients receiving anti-inflammatory drugs (nonsteroidal): patients with chronic pain (non migraine, no anti-inflammatory drug therapy) had lower ME levels than patients without pain. The data are discussed in relation to animal models of chronic pain.

Randomized study of minocycline + gentamicin compared with metronidazole + gentamicin for prophylaxis or treatment of mixed infections in abdominal surgery.

Seventy patients admitted for abdominal surgery requiring short-term perioperative prophylaxis were randomized to receive minocycline + gentamicin or metronidazole + gentamicin. Thirty patients were considered to be infected at the time of surgery and were treated with the same regimen. In the prophylactic cohort, one patient from each group developed postoperative fever. One patient receiving minocycline developed a wound infection. The overall infection rate was 2.6%. In the treatment cohort, it appeared that the patients receiving metronidazole had more severe underlying diseases than those receiving minocycline. Consequently, more postoperative non-infectious complications were observed in the former. Minocycline + gentamicin appeared at least as effective than metronidazole + gentamicin in preventing postoperative infectious complications associated with abdominal surgery or in treating intra-abdominal infections.

Simultaneous evaluation of mRNAs of dopamine ?-hydroxylase, tyrosine hydroxylase and proenkephalin a from three human pheochromocytomas.

Using the rabbit reticulocyte cell-free translation system, the relative proportions of in vitro translatable mRNAs of three proteins in three human pheochromocytomas: tyrosine hydroxylase (TH), dopamine ?-hydroxylase (DBH) and proenkephalin A have been compared. TH expression appeared rather constant in the three tumors. In contrast, those of DBH and proenkephalin A were more variable. Though the actual level of each mRNA was not determined, the identical value of DBH/proenkephalin A mRNAs ratio in the three tumors could suggest a coordination in the expression of these two proteins.

In vitro translation of human pheochromocytoma messenger RNAs: characterization of tyrosine-hydroxylase and dopamine-beta-hydroxylase.

mRNAs extracted from human pheochromocytoma were translated in vitro in a lysate of a rabbit reticulocytes. Two enzymes of the biosynthetic pathway of the catecholamines, tyrosine-hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), were characterized as translation products after immunoprecipitation by specific antisera and electrophoretic analysis. The precursor of TH is a polypeptide having a molecular mass of 62,000 identical to that found for the mature protein. The molecular mass of the precursor of DBH 73,000 while that of the mature form is 79,000. TH and DBH have been translated from mRNAs having sedimentation coefficients of 22S and 25S, respectively.

Simultaneous evaluation of the catecholamine pathway and three opioid peptide-producing systems in human pheochromocytomas.

Tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) activities, dopamine (DA), noradrenaline (NA), adrenaline (A), met 5-enkephalin (Met-Enk), leu5-enkephalin (Leu-Enk), dynorphin (Dyn) and beta-endorphin (beta-end) were measured simultaneously in ten human pheochromocytomas = 1 - TH activity was highly variable, from 22 to 2220 U/g tissue. 2 - DBH activity, in contrast, was rather constant, from 96 to 582 U/g. 3 - Catecholamines (A and NA) concentrations showed only small variations. 4 - The four opioid peptides were detected in all cases and exhibited a wide range of tissue concentrations (Enk much greater than Dyn greater than beta-end). 5 - Met-Enk and Leu-Enk concentrations were highly correlated; no correlation was observed with the other opioid peptides. 6 - A very strong correlation was observed between enkephalins concentrations and both catecholamines concentrations and DBH activities. These results are discussed in term of the significance of the co-localization of these various biologically active substances, principally with regard to the possible regulation of catecholamine synthesis by opioid peptides and conversely.

The final step of aldosterone biosynthesis requires reducing power. It is not a dehydrogenation.

A mitochondrial preparation from adult duck adrenal gland was used to study the mechanism (dehydrogenation or other) of the last step of aldosterone biosynthesis (18-oxidation) by incubation of tritiated 18-hydroxycorticosterone. Results show that the role of citric acid cycle metabolites is to provide reducing power. When reducing power is provided by malate, which yields NADH or NADPH directly, the reoxidation of reduced coenzymes in the oxidative phosphorylation chain is not necessary. In the presence of succinate, the oxidative phosphorylation chain is required, but only to provide ATP. Stimulation of the reaction by low concentrations of KCN in the presence of malate shows that the reducing power is not used in the oxidative phosphorylation chain. These data suggest that the reaction is not a dehydrogenation and that the reducing power is used in a pathway competing with the respiratory chain, most probably a hydroxylating pathway, in mitochondria.

[Aldosterone in primary hyperaldosteronism]. / L'aldostérone dans l'hyperaldostéronisme primaire.

The conditions which must be respected to ensure the validity of the biochemical diagnostic criteria of primary hyperaldosteronism, conditions of blood sampling, timing posture and age of the patient, sodium intake and intercurrent drug therapy. As none of the tests is 100 p. 100 specific in distinguishing adrenal adenoma from hyperplasia, an association of several investigations has to be used. In cases of adenoma, the authors recommend the investigations which demonstrate the autonomy of secretion and the prevalence of circadian rhythm over the influence of change in posture. The measurement of aldosterone levels may be completed by that of its precursor, 18-hydroxy-corticosterone (18 OH CS).